Surgery is the only certain cure for cancer; however, its curative ability is compromised by the potential of leaving behind microscopic traces of the tumor, known as margins. In breast cancer, for example, there is a 20% recurrence rate after breast-conserving surgery (lumpectomy) due to missed margins. A beta camera capable of surveying the tumor bed, intraoperatively, and imaging visually undetectable, minute amounts of cancer cells, could significantly reduce recurrence rate of many cancers and increase survival. In addition, this beta camera may enable more breast cancer patients to become candidates for breast saving lumpectomies and improve the psychological recovery from breast cancer.
Surgery is an important mode of treatment of prostate cancer. However, several problems remain. Complete local resection of cancerous tissue is not possible in some cases since normal and prostate cancer tissues are not visually distinguishable. In approximately 30% of cases the margins of resection are involved (or positive). Unfortunately, this finding is currently made by the pathologist from the resected prostate, well after the surgery, when there is little that can be done to rectify the situation. Further, assessment of lymph nodes is important in staging the cancer. This is done by multiple node dissections and pathological evaluations in the vast majority of patients, which results in increased morbidity, operative time, and cost. Currently, trans-rectal biopsies, in post-prostatectomy patients with elevated PSA, are done with ultrasound guidance. However, often no suspicious lesion is seen and biopsies are little more than random samples. As a result, there is a low sensitivity rate.
Vulnerable atherosclerotic plaques are the major cause of sudden cardiac death. Detection of this type of plaques is a major challenge in cardiology. Various radiopharmaceuticals have been developed to this date with preferential uptake in vulnerable plaques. Vulnerable plaque (VP) is atherosclerotic plaque that is prone to disruption, causing thrombosis, which often leads to a clinical event. Autopsy studies have demonstrated that the majority of cases of sudden death are caused by occlusive coronary thromboses that are associated with an underlying ruptured plaque. From such autopsy studies, much has been learned about the morphological features that are common to VP. Those histologic characteristics include a thin fibrous cap, an underlying lipid pool, and an abundance of inflammatory cells.
Even with today's best available technology an unacceptably high incidence of cardiovascular events remains even after aggressive therapy. Novel approaches to prevent myocardial infarctions are therefore needed. It is proposed that one of the most effective methods to prevent MI would be to stabilize vulnerable plaque before they rupture. However, currently available systemic therapies are able to lower the risk of plaque rupture by only 20-40%, leaving the vast majority of vulnerable plaques ripe for rupture. As such, it is crucial that vulnerable plaques are localized such that local plaque-stabilizing therapies can be delivered. However, currently available technologies are not able to detect vulnerable plaques. This may be due to the fact that available technologies rely on identifying structural criteria to differentiate the common stable plaque from the rupture-prone vulnerable plaque. Indeed, the most commonly employed method for plaque characterization is coronary arteriography, a method which qualifies plaques based on the degree to which they impinge on and thus narrow the vessel lumen. Multiple angiographic studies that have examined ruptured plaques have found that they are most often associated with insignificant luminal narrowing prior to their rupture. Therefore, technologies that rely on identifying luminal narrowing are not able to identify vulnerable plaques with acceptable sensitivity.
Further, inflammation is particularly important in the development and progression of atherothrombosis. It is now well-established that atherosclerosis is an inflammatory disease. Histopathological data has confirmed the critical association of plaque inflammation and rupture. Numerous studies demonstrate an abundance of inflammatory cells (T cells and macrophages) within ruptured plaques. Moreover, several large studies have shown a strong association between inflammatory biomarkers and subsequent events. Positron emission tomography (PET) may represent the most promising non-invasive imaging technology for the detection of inflammation in humans. PET imaging with 18F-Flurodeoxyglucose (FDG) has been used extensively in humans to detect metabolically active tissues such as neoplasms, autoimmune disease, and infection. Numerous studies demonstrate that FDG uptake is increased in inflamed tissues such as tumors and infectious foci. Autoradiographic studies show that FDG localizes to macrophage-dense regions within chronic inflammatory lesions and within macrophages surrounding malignant foci.
F-18 atoms emit positrons (beta rays) that in turn generate gamma rays. Gamma rays travel tens of cm in tissue, while beta rays have a range of ˜2 mm. Beta emitting isotopes are ideal for intraoperative imaging since background radiation will not interfere with the identification of margins. Until now, beta cameras have suffered from serious flaws that prevent their general use in cancer surgery or in vivo diagnostic procedures. The thin shielding required for positron detection provides insufficient insulation from the high voltage photomultiplier tubes (PMTs) and the long fiber-optic coupling used to separate the high voltage from the patient can greatly reduces sensitivity.
Numerous studies have demonstrated PET's enhanced sensitivity and specificity for identifying tumors as compared to more conventional techniques (Finkelstein S E, Carrasquillo J A, Hoffman J M, Galen B, Choyke P, White D E, Rosenberg S A, Sherry R M. “A Prospective Analysis Of Positron Emission Tomography And Conventional Imaging For Detection Of Stage IV Metastatic Melanoma In Patients Undergoing Metastasectomy”, Ann Surg Oncol, 11, p 731-738 (2004); Gulec S A, Faries M B, Lee C C, Kirgan D, Glass C, Morton D L, Essner R. “The Role Of Fluorine-18 Deoxyglucose Positron Emission Tomography In The Management Of Patients With Metastatic Melanoma: Impact On Surgical Decision Making”, Clin Nucl Med, 28 p 961-965 (2003); Benard F, Turcotte E. “Imaging In Breast Cancer: Single-Photon Computed Tomography And Positron-Emission Tomography”, Breast Cancer Res, 7, p 153-162, (2005)). Usually, PET is performed after IV injection of F-18 labeled fluorodeoxy-glucose (FDG), a glucose analog that is transported into cells but can't complete its metabolism like glucose, and hence accumulates in the cells. Cancer cells accumulate more FDG than normal cells; therefore they become more radioactive than the surrounding normal tissue. The positrons that are emitted by F-18 travel a short distance in tissue (˜1 mm) and then pair up with an electron and annihilate to two high-energy gamma rays. These high-energy gamma rays each have 511 keV energy, and are emitted simultaneously and back-to-back (at a 180 degree angle to each other). The coincidence detection of these emissions by detectors of a PET scanner determines a line along which the F-18 decay occurred (called the line of response). During the PET scan, a collection of these lines will accumulate in the computer of the PET scanner. Using a tomographic algorithm, a distribution map of FDG accumulation is generated by the collection of lines of responses.
A prerequisite for the accurate identification of cancer with PET is the ability of the radiation source to localize within the tumor, with only minimal or no uptake in adjacent normal tissue, necrotic tissue, or healing tissue. A large number of radioisotopes emit positrons. Notable among them are radioisotopes of carbon, nitrogen, oxygen and fluorine (substituted for hydrogen in many compounds). These are the building blocks of biologic matter. Therefore, the choice for making positron emitting radioisotopes is large. To date, more than 500 radiochemicals have been developed with positron emitting radioisotopes (Quon A, Gambhir S S. “FDG-PET And Beyond: Molecular Breast Cancer Imaging”, J Clin Oncol, 23, p 1664-1673 (2005)). Although there are a variety of radioisotopes that would be useful for PET imaging based on metabolic properties of malignancy, so far only FDG has gained universal acceptance as a cancer-seeking agent. The use of FDG is based on the concept that tumor tissues grow generally faster than normal tissues, and thus have an increased rate of glucose metabolism. The FDG molecule is transported into cells by facilitative glucose transporters, such as GLUT-1, and is phosphorylated to PDG-6 phosphate by hexokinase (Luigi A, Caraco C, Jagoda E, Eckelman W, Neumann, Ronald. Glut-1 And Hexokinase Expression: Relationship With 2-Fluoro-2-Deoxy-D-Glucose Uptake In A431 And T47d Cells In Culture”, Cancer Res, 59, p 4709-4714 (1999)). Some cancers also have reduced rates of glucose-6-phosphate metabolism accentuating the phosphorylated deoxyglucose into tumor tissue (Chung J K, Lee Y J, Kim S K, Jeong J M, Lee D S, Lee M S. “Comparison Of [18F]Fluorodeoxyglucose Uptake With Glucose Transporter-1 Expression And Proliferation Rate In Human Glioma And Non-Small-Cell Lung Cancer”, Nucl Med Commun, 25, p 11-17 (2004); Pugachev A, Ruan S, Carlin S, Larson S, Campa J, Ling C, Humm J. “Dependence Of FDG Uptake On Tumor Microenvironment”, Int J Rad Oncol Biol Phys, 62, p 545-553 (2005)). This intermediary is trapped in cancer cells because the dephosphorylation reaction is either slow or absent.
The greater uptake of FDG and lower levels of metabolism in more aggressive tumors lead to improved imaging of particular cancers; i.e., more accurate staging. FDG avidity is determined by glycolytic activity of the tumor and the viable tumor volume. Individual cancer types may show significant variability in terms of FDG avidity. Even in the same patient, different lesions may have different degrees of FDG uptake. FDG metabolism and clearance occurs at a much faster rate in normal tissues than tumor tissue, and thus tumor-to-background ratios improves with time resulting in better lesion detection when imaging is delayed. Boerner et al. have shown that tumor-to-non-tumor and tumor-to-organ ratios were significantly higher for the images taken at 3 hours post-injection than for the 1.5-hour images, and lesion detectability was 83% in 1.5-hour images compared to 93% in 3-hour images in breast cancer patients. Although more delayed intervals between FDG injection and imaging might compromise image quality due to lower count rates, this is much less of an issue with an FDG sensitive probe. Longer intervals may accentuate the tumor to background ratios, and further improve FDG detection. Important contributors to the background radiation are the sites of physiologic FDG uptake. The in situ tumor to background ratios is strongly affected by the surrounding areas of physiologic uptake or accumulation. The brain uptake in the head and neck region, cardiac uptake in the chest, kidney uptake and the accumulation inside the bladder in abdomen and pelvis affect the in situ tumor to background ratios.
Gritters and colleagues (Gritters L S, Francis I R, Zasadny K R, Wahl R L. “Initial Assessment Of Positron Emission Tomography Using 2-Flourine-18-Flouro-2-Deoxy-D-Glucose In The Imaging Of Malignant Melanoma”, J Nucl Med, 34, p 1420-1427 (1933)) found PET to be highly accurate for identifying cutaneous melanoma metastases. A number of other investigators have also found PET to be both sensitive and specific for metastatic melanoma. For distant metastases, numerous studies have shown PET to have equal or superior sensitivity to CT, MRI, and ultrasound (Schwimmer J, Essner R, Patel A, Jahan S A, Shepherd J E, Park K, Phelps M E, Czernin J, Gambhir SS. “A Review Of The Literature For Whole-Body FDG PET In The Management Of Patients With Melanoma”, Quarterly J Nucl Med, 44, p 153-167, (2000); Finkelstein, SE, Carrasquillo J A, Hoffman J M, Galen B, Choyke P, White D E, Rosenberg S A, Sherry R M. “A Prospective Analysis Of Positron Emission Tomography And Conventional Imaging For Detection Of Stage IV Metastatic Melanoma In Patients Undergoing Metastasectomy”, Ann Surg Oncol, 11, p 731-738 (2004); Kaleya R N, Heckman J T, Most M, Zager J S. “Lymphatic Mapping And Sentinel Node Biopsy: A Surgical Perspective”, Semin Nucl Med. 35, p 129-134, (2005)). While melanoma is more likely to metastasize to the brain, lung, or liver, the pattern is unpredictable and so whole-body functional imaging is most suitable. Numerous studies have shown the value of PET in the management of patients with advanced melanoma, with treatment plan changing in 15-50% of cases (Gulec S A, Faries M B, Lee C C, Kirgan D, Glass C, Morton D L, Essner R. “The Role Of Fluorine-18 Deoxyglucose Positron Emission Tomography In The Management Of Patients With Metastatic Melanoma: Impact On Surgical Decision Making”, Clin Nucl Med, 28, p 961-965 (2003); Damian D L, Fulham M J, Thompson E, Thompson J F. “Positron Emission Tomography In The Detection And Management Of Metastatic Melanoma”, Melanoma Res, 6, p 325-329 (1996); Tyler D S, Onaitis M, Kherani A, Hata A, Nicholson E, Keogan M, Fisher S, Coleman E, Seigler H F. “Positron Emission Tomography Scanning In Malignant Melanoma—Clinical Utility In Patients With Stage III Disease”, Cancer, 89, p 1019-1025 (2000); Jadvar H, Johnson D L, Segall G M. “The Effect Of Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography On The Management Of Cutaneous Malignant Melanoma”, Clin Nucl Med, 25, p 48-51 (2000; Stas M, Stroobants S, Dupont P, Gysen M, Van Hoe L, Garmyn M, Mortelmans L, De Wever I. “18-FDG PET Scan In The Staging Of Recurrent Melanoma: Additional Value And Therapeutic Impact”, Melanoma Res, 12, p 479-490, (2002); Wong C S, Silverman D H, Seltzer M, Schiepers C, Ariannejad M, Gambhir S S, Phelps M E, Rao J, Valk P, Czernin J. “The Impact Of 2-Deoxy-2[18F] Fluoro-D-Glucose Whole Body Positron Emission Tomography For Managing Patients With Melanoma: The Referring Physician's Perspective”, Mol Imaging Biol, 4, p 185-190 (2002)). CT is, however, superior to PET in the detection of small pulmonary metastases, possibly due to respiratory motion (Gritters et al, ibid; Kumar et al, ibid; Rinne D, Baum R P, Hor G, Kaufmann R. “Primary Staging And Follow-Up Of High Risk Melanoma Patients With Whole-Body F-18-Fluorodeoxyglucose Positron Emission Tomography—Results Of A Prospective Study Of 100 Patients”, Cancer, 82, p 1664-1671, (1998)). Neither lab tests nor imaging have been shown to be useful in detecting recurrence in asymptomatic patients. In patients with known recurrence PET has been shown to detect additional metastases and alter treatment planning. Stas et al. (Stas M, Stroobants S, Dupont P, Gysen M, Van Hoe L, Garmyn M, Mortelmans L, De Wever I. “18-FDG PET Scan In The Staging Of Recurrent Melanoma: Additional Value And Therapeutic Impact”, Melanoma Res, 12, p 479-490 (2002) found the sensitivity, specificity, and accuracy of PET to be 85%, 90%, and 88%, respectively as compared to 81%, 87%, and 84% with conventional imaging. Fuster et al (Fuster D, Chiang S, Johnson G, Schuchter L M, Zhuang H M, Alavi A. “Is F-18-FDG PET More Accurate Than Standard Diagnostic Procedures In The Detection Of Suspected Recurrent Melanoma?” J Nucl Med. 45, p 1323-1327 (2004)) studied 156 patients with known or suspected recurrence and found the sensitivity, specificity, and accuracy of PET to be 74%, 86%, and 81% respectively compared to 58%, 45%, and 52% for conventional imaging.
FDG-PET imaging is becoming the method of choice for staging of breast cancer as well as for the detection of recurrent disease (Quon A, Gambhir SS. “FDG-PET And Beyond: Molecular Breast Cancer Imaging”, J Clin Oncol, 23 p 1664-1673 (2005)), the location of metastases (Lonneux M, Borbath I, Berliere M, et al. “The Place Of Whole-Body PET FDG For The Diagnosis Of Distant Recurrence Of Breast Cancer”, Clin Positron Imaging, 3, p 45-49 (2000)), and the monitoring of responses to radiation and chemotherapy. It is not yet widely used in primary diagnosis, though, due to significant variation in FDG avidity based on tissue pathology and tumor size (Luigi et al, ibid). Noninvasive breast cancer has been previously shown to be poorly imaged by FDG-PET (Wu D, Gambhir SS. “Positron Emission Tomography In Diagnosis And Management Of Invasive Breast Cancer: Current Status And Future Perspectives”, Clin Breast Cancer, 4(Suppl 1), pS55-S63, (2003)) and the majority of FDG-PET research studies in the literature have been performed on patients with invasive breast cancer. There are significant variations between studies. The overall specificity of FDG-PET is relatively high, but false-positives do occur in some benign inflammatory conditions and fibroadenomas (Pelosi E, Messa C, Sironi S, et al. “Value Of Integrated PET/CT For Lesion Localization In Cancer Patients: A Comparative Study”, Eur J Nucl Med Mol Imaging, 31, p 932-939 (2004); Avril N, Rose C A, Schelling M, et al. “Breast Imaging With Positron Emission Tomography And Fluorine-18 Fluorodeoxyglucose: Use And Limitations.” J Clin Oncol, 18, p 3495-3502 (2000)).
Invasive breast cancer includes multiple histologic types including infiltrating ductal, infiltrating lobular, and combined infiltrating ductal and lobular carcinoma. Infiltrating ductal carcinoma has a higher level of FDG uptake and therefore is detected at a significantly higher sensitivity than infiltrating lobular breast cancer (Zhao S, Kuge, Y, Mochizuki T, Takahashi T, Nakada K, Sato M, Takei T, Tamaki N. “Biologic Correlates Of Intratumoral Heterogeneity In 18F-FDG Distribution With Regional Expression Of Glucose Transporters And Hexokinase-II In Experimental Tumor”, J Nucl Med, 46, p 675-682 (2005); Amthauer H, Denecke T, Rau B, Hildenbrandt B, Hunerbein M, Ruf J, Scheider U, Gutberlet M, Schlar P M, Felix R, Wust P. “Response Prediction By FDG-PET After Neoadjuvant Radiochemotherapy And Combined Regional Hyperthemia Of Rectal Cancer: Correlation With Endorectal Ultrasound And Histopathology”, Eur J Nucl Med Mol Imaging, 31, p 811-819 (2004)). This suggests that tumor aggressiveness is not the sole determinant of FDG uptake but that the mechanism of the variable FDG uptake by breast cancer cells is likely modulated by multiple factors including glucose transport-1 (GLUT 1) expression, hexokinase I (Hex-1) activity, tumor microvessel density, amount of necrosis, number of lymphocytes, tumor cell density, and mitotic activity index (Bos R, van Der Hoeven J J, van Der Wall E, et al. “Biologic Correlates Of [F18]Fluorodeoxyglucose Uptake In Human Breast Cancer Measured By Positron Emission Tomography”, J Clin Oncol, 20, p 379-387, (2002)).
Image-guided core biopsy has the advantage of being the least invasive, most comfortable for the patient, and least costly method to determine the nature of image-detected abnormalities. The issue of a benign finding that apparently is not consistent with the clinical and radiographic findings has been most carefully studied in the management of breast abnormalities, which may be palpable or only observed by various imaging techniques. When a benign histologic diagnosis appears to be consistent with both the clinical findings and the radiographic features (the “triple test”) the likelihood of missing malignant disease is minimized and follow-up examinations rather than surgical biopsy are recommended.
In the increasingly frequent scenario of pre-clinical, image-detected lesions, physical examination is not helpful in determining concordance; thereby leading to considerable uncertainty as to whether the area of interest has been appropriately sampled. Detecting radioactivity in the core sample obtained from a PET-positive abnormality would be a great advance in confirming accurate sampling, and therefore, definitive histologic diagnosis. The increasing sensitivity of imaging modalities, including magnetic resonance (MRI), computed tomography (CT), and positron emission tomography (PET) has resulted in the identification of abnormalities prior to the development of clinical manifestations. The nature of such abnormalities, which may represent primary tumors or metastatic lesions, must be determined. Minimally invasive, image-guided, core-needle biopsies are generally the first diagnostic approach. If a benign diagnosis is rendered, the clinician, in consultation with the radiologist and pathologist, must determine whether the finding is concordant with the clinical history and the configuration of the image-detected abnormality. Non-concordance implies the possibility of a sampling error, which often leads to a recommendation for open, surgical biopsy.
Examples of probes for intraoperative radiation detection which might be used in the procedures described herein include:
Scintillator-PMT systems, that use vacuum tube PMTs and scintillation crystals such as NaI(Tl),
Scintillator-PIN diode systems that use PIN diodes as light detectors and then couple them to a scintillator with emissions around ˜500 nm wavelength (such as CsI). The PIN diode has a gain of one (1) and therefore needs very low noise and high gain amplifiers,
Cd—Te semiconductor detectors, that convert the energy from radiation directly to an electronic pulse, or
Zn—Cd—Te semiconductor detectors that convert the energy from radiation directly to an electronic pulse.
Applicant's existing beta camera, developed in the early 1990s utilizes a position-sensitive photomultiplier tube (Hamamatsu 8520-00-12) that is optically coupled directly to a 1 mm thick sheet of plastic scintillator. A thin foil of aluminum Mylar (50 micron thick) is used to cover the front of the scintillator, to make it light-tight, while allowing positrons to enter the scintillator. This camera operates at 1200 Volts (F. Daghighian, P. Shenderov, B. Eshagian. “Interoperative Beta Cameras”. J. Nucl. Med., 446 (May 1995). Although the whole camera is well insulated electrically for ex-vivo use, to provide the level of insulation needed for its safe use in the surgical site is an impossible task. An improvement to the electrical safety was accomplished by building a flexible beta camera comprising a 2×1.5×150 cm3 imaging grade array of optical fibers (each 100 microns thick) located between the sheet of plastic scintillator and the position sensitive PMT. The optical fibers act as an insulator, but light loss in this fiber bundle is large and degrades the sensitivity. A sub-millimeter resolution with a sensitivity of 4000 cps/microCi is achievable with this camera. Tornai et al. (M. P. Tornai, L. R. MacDonald, C. S. Levin, S. Siegel, E. J. Hoffman, “Design Considerations And Initial Performance Of A 1.2 Cm2 Beta Imaging Intra-Operative Probe.” IEEE Trans. Nuc. Sci., 43 (4), p 2326 (1996)) built a similar flexible beta camera and measured a line spread function of 0.5 mm for their 1.08 cm FOV camera, and a transmission image consisting of 0.5 mm holes 0.6 mm apart was successfully imaged. However, the sensitivity of this camera was not acceptable for surgical procedures. Yamamoto and colleagues built cameras with 10 and 20 mm diameters, and measured 0.8 mm and 0.5 mm FWHM, respectively (S. Yamamoto, C. Seki, K. Kashikura, H. Fujita, T. Matsuda, R. Ban, I. Kanno, “Development of a High Resolution Beta Camera for a Direct Measurement of Positron Distribution on Brain Surfaces.” IEEE Trans. Nuc. Sci. 44 (4) p 1538 (1997)
Various solid state detectors have been proposed. Tornai and colleagues developed a prototype silicon strip detector, though this was never incorporated into a surgical device (M. P. Tornai, B. E. Patt, J. S. Iwanczyk, C. R. Tull, L. R. MacDonald, E. J. Hoffman, “A Novel Silicon Array Designed For Intraoperative Charged Particle Imaging.” Medical Physics, 29 (11), p 2529 (2002)). Janacek et al. developed a positron-sensitive intravascular probe which incorporated a multi-element linear silicon array (M. Janacek, E. J. Hoffman, C. R. Tull, B. E. Patt, J. S. Iwanczyk, L. R. MacDonald, G. J. Maculewicz, V. Ghazarossian, H. W. Strauss, “Multi-Element Linear Array Of Silicon Detectors For Imaging Beta Emitting Compounds In The Coronary Arteries.” Proc. IEEE NSS/MIC (2002). The disadvantage of silicon based beta cameras is that they do not have internal gain as does an SSPM, and they bring the electrical charge onto the surface of the beta camera. Therefore they are not electrically safe. A shortcoming of using CdTe or CdZnTe for constructing a beta camera is that they have high atomic numbers and high densities; therefore, they are more sensitive to unwanted background gamma rays than plastic scintillators (density of 1 and atomic number of 6).
Introduced in 2002, solid state photomultipliers have been used primarily in high energy and astrophysics experiments where very high sensitivity light detection is required (P. Buzhan, B. Dolgoshein, A. Ilyin, V. Kantserov, V. Kaplin, A. Karakash, A. Pleshko, E. Popova, S. Smimov, Yu. Volkov, L. Filatov, S. Klemin, F. Kayumov, “The Advanced Study of Silicon Photomultiplier”, ICFA Instrumentation Bulletin, 23 (Fall 2001); Buzhan P, Dolgoshein B, Filatov L et al. “Silicon Photomultiplier And Its Possible Applications”, Nuclear Instruments and Methods in Physics Research A, 504 p 48-52 (2003). A silicon photomultiplier is a large assembly of avalanche photodiodes operating in Geiger mode. Each detector, which can be as small as 1 mm×1 mm, consists of an array of (˜600) micropixels connected in parallel (FIG. 1)). The micropixels act individually as binary photon detectors, in that an interaction with a single photon causes a Geiger discharge. Each micropixel “switch” operates independently of the others, and the detector signal is the summed output of all micropixels within a given integration time. When coupled to a scintillator, such as by an optical glue, the SSPM detects the light produced in the scintillator by incident radiation, giving rise to a signal proportional to the energy of the radiation.
A recent development is a solid state or silicon photomultiplier (SSPM, or SiPM) developed by a team from the Moscow Engineering and Physics Institute (B Dolgoshein Int. Conf. on New Developments in Photodetection (Beaune, France) June 2002) together with Pulsar Enterprise in Moscow. The device comprises a large number of microphoton counters (1000/mm2) which are located on a common silicon substrate and have a common output load. Each photon counter is a small (20-30 μm square) pixel with a depletion region of about 2 μm. They are decoupled by polysilicon resistors and operate in a limited Geiger mode with a gain of approximately one million. This means that the SiPM is sensitive to a single photoelectron, with a very low noise level. Each photon counter operates digitally as a binary device. However the assembly of multiple SiPM is an analogue detector with the capability to measure light intensity within a dynamic range of about 1000/mm2 and has high photon capability.
The photon detection efficiency of the SSPM is at about the same level as photomultiplier tubes (PMTs) in the blue region (20%), and is higher in the yellow-green region. The device has very good timing resolution (50 ps r.m.s. for one photoelectron) and shows good temperature stability. It is also insensitive to magnetic fields. These characteristics mean that the SSPM can be used in place of other known photodetectors (e.g., PMT, APD, HPD, VLPC). The main advantage of the SSPM is its small size (1×1 mm) and its low operating voltage of ˜60 V. These characteristics render SSPM ideal for use in intraoperative and intra-luminal radiation detection probes and cameras.
One currently proposed medical applications for SSPM is in a small field of view PET scanner that can work in high magnetic fields of an MRI scanner (Rubashov, I. B., U.S. Pat. No. 6,946,841).